Substituted derivatives of cyclohexan-1,4-diamine, method for their preparing and drug

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of cyclohexan-1,4-diamine of the general formula (I): possessing binding property with ORLI receptors and showing homology to opioid μ-, κ- and δ-receptors. Compounds can be used for preparing drugs possessing analgesic effect. In the formula (I) R1 and R2 mean independently of one another (C1-C8)-alkyl, or residues R1 and R2 form in common a ring and mean -CH2-CH2NR6CH2CH2 or -(CH2)3-6 wherein R means (C1-C8)-alkyl; R3 means phenyl, naphthyl or 5-membered sulfur-containing heteroaryl wherein each of them is unsubstituted or monosubstituted with halogen atom, or unsubstituted phenyl added through saturated unsubstituted (C1-C4)-alkyl group; R4 means hydrogen atom (H), saturated (C1-C8)-alkyl or -C(X)R7 wherein X means oxygen (O) or sulfur (S) atom; R means H or (C1-C8)-alkyl either unsubstituted phenyl or phenyl substituted with halogen atom; R5 means (C3-C8)-cycloalkyl, adamantyl, aryl or 5-membered heteroaryl comprising 1-3 heteroatoms chosen from nitrogen, oxygen or sulfur and condensed with one or two benzene rings and wherein each of them is unsubstituted or monosubstituted with a substitute chosen from halogen atom, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or -CHR11R12, -CHR11-CH2R12, -CHR11-CH2-CH2R12, -CHR11-CH2-CH2-CH2R12, -C(Y)R12 wherein Y means O or H2; R11 means H, saturated, linear or branched (C1-C7)-alkyl, saturated or unsaturated, linear or branched, mono- or multisubstituted either unsubstituted -C(O)O-(C1-C6)-alkyl; R12 means phenyl or 5-membered heteroaryl comprising 1-3 heteroatoms chosen from nitrogen, oxygen or sulfur condensed with one or two benzene rings each of them is unsubstituted or mono- or multisubstituted and wherein in values R11 and R12 substituted of alkyl, phenyl or heteroaryl are chosen from halogen atom, lower alkyl, lower alkoxy, hydroxy, trifluoromethyl or benzyloxy; or R4 and R5 form in common 5-membered nitrogen-containing heterocycle that represents unsaturated, monosubstituted lower alkoxycarbonyl-lower alkyl, halogen atom, or it is unsubstituted and condensed with benzene ring under condition that if R means substituted or unsubstituted phenyl and at least one R1 or R2 means (C1-C8)-alkyl then R4 can't mean alkyl, and R3 and R5 can't form in common heterocycle, or if R3 means unsubstituted phenyl and R1 and R2 mean in common -(CH2)5 then R4 means H or (C1-C8)-alkyl; Y means O, and R5 doesn't mean (C1-C6)-alkyl. Also, invention relates to a method for synthesis of compounds of the formula (I) and a drug.

EFFECT: valuable medicinal properties of compounds.

40 cl, 1 tbl, 94 ex

 

The text descriptions are given in facsimile form.

1. Substituted derivatives of cyclohexane-1,4-diamine of the General formula I

in which R1and R2independently of one another denote With1-8alkyl, or the residues R1and R2together form a ring and denote CH2CH2NR6CH2CH2or (CH2)3-6where R6stands With1-8alkyl,

R3denotes phenyl, naphthyl or a five-membered sulfur-containing heteroaryl, each of which is either unsubstituted or one-deputizing halogen, or unsubstituted phenyl, attached through unsubstituted saturated With1-4alkyl group,

R4oboznachaet is H, With1-8alkyl, which is saturated, or C(X)R7,

where X denotes O or S,

R7denotes N or C1-8alkyl or phenyl, which is unsubstituted or substituted with halogen,

R5stands With3-8cycloalkyl, substituted, aryl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and condensed with one or two benzene rings, each of which is unsubstituted or one-deputizing Deputy selected from halogen, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or-CHR11R12, -CHR11-CH2R12, -CHR11-CH2-CH2R12, -CHR11-CH2-CH2-CH2R12, -C(Y)R12,

where Y denotes O or H2,

R11denotes H, C1-7alkyl, which is saturated branched or unbranched, or C(O)O-C1-6alkyl, which is saturated or unsaturated, branched or unbranched, single or mnogosloinym or unsubstituted, and

R12denotes phenyl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, condensed with one or two benzene rings, each of which is unsubstituted or one - or mogosa emenim,

thus the values of R11and R12the substituents of the alkyl, phenyl or heteroaryl selected from halogen, lower alkyl, lower alkoxy, hydroxy, trifloromethyl or benzyloxy; or

R4and R5together form a five-membered nitrogen-containing heterocycle, which is unsaturated, one-deputizing lower alkoxycarbonyl-lower alkyl, halogen or unsubstituted, and which is condensed with benzene ring,

provided that if R3denotes a substituted or unsubstituted phenyl and at least one of the residues R1or R2stands With1-8alkyl, R4cannot denote alkyl, and R4and R5can't work together to form a heterocycle, or, if R3denotes unsubstituted phenyl and R1and R2together denote (CH2)5, R4denotes N or C1-8alkyl, Y represents Oh, R5does not denote With1-6alkyl, in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically compatible acids or cations.

2. Emesene derivatives, cyclohexane-1,4-diamine according to claim 1 of General formula I

in which R1 , R2and R3have specified in claim 1 values

R4denotes N, C(X)R7,

where X denotes O or S,

R7denotes N or C1-8alkyl or phenyl, which is unsubstituted or substituted with halogen,

R5stands With3-8cycloalkyl, aryl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and condensed with one or two benzene rings, each of which is unsubstituted or one-deputizing, Deputy selected from halogen, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or-CHR11R12, -CHR11-CH2R12, -CHR11-CH2-CH2R12, -CHR11-CH2-CH2-CH2R12, -C(Y)R12,

where Y denotes O or H2,

R11denotes H, C1-7alkyl, which is saturated branched or unbranched, or C(O)O-C1-6alkyl, which is saturated or unsaturated, branched or unbranched, single or mnogosloinym or unsubstituted, and

R12denotes phenyl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, condensed with one or two benzene rings, each of which is nezametnymi one or mnogosloinym,

thus the values of R11and R12the substituents of the alkyl, phenyl or heteroaryl selected from halogen, lower alkyl, lower alkoxy, hydroxy, trifloromethyl or benzyloxy, in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically compatible acids or cations.

3. Substituted derivatives of cyclohexane-1,4-diamine according to claim 1 of General formula I

in which R1and R2independently of one another denote With1-8alkyl,

R3have the above in claim 1 values

R4denotes N, C(X)R7,

where X denotes O or S,

R7denotes N or C1-8alkyl or phenyl, which is unsubstituted or substituted with halogen,

R5stands With3-8cycloalkyl, aryl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and condensed with one or two benzene rings, each of which is unsubstituted or one-deputizing Deputy selected from halogen, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or-CHR11R12, -CHR11-CH2R12, -CHR11 -CH2-CH2R12, -CHR11-CH2-CH2-CH2R12, -C(Y)R12,

where Y denotes O or H2,

R11denotes H, C1-7alkyl, which is saturated branched or unbranched, or C(O)O-C1-6alkyl, which is saturated or unsaturated, branched or unbranched, single or mnogosloinym or unsubstituted, and

R12denotes phenyl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and condensed with one or two benzene rings, each of which is unsubstituted or one - or mnogosloinym,

thus the values of R11and R12the substituents of the alkyl, phenyl or heteroaryl selected from halogen, lower alkyl, lower alkoxy, hydroxy, trifloromethyl or benzyloxy, in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically compatible acids or cations.

4. Substituted derivatives of cyclohexane-1,4-diamine according to claim 1 of General formula I

in which R1, R2, R4and R5have specified in claim 1 values, and

R3 represents a five-membered sulfur-containing heteroaryl, which is either unsubstituted or one-deputizing halogen, or unsubstituted phenyl, attached through unsubstituted saturated With1-4alkyl group,

in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically compatible acids or cations.

5. Substituted derivatives of cyclohexane-1,4-diamine according to claim 1 of General formula I,

in which the residues R1and R2together form a ring and denote CH2CH2NR6CH2CH2or (CH2)3-6where R6stands With1-8alkyl,

and the remaining substituents have specified in claim 1 values

in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically sovmestimye acids or cations.

6. Substituted derivatives of cyclohexane-1,4-diamine according to claim 1, 2 or 4, wherein R1and R2independently of one another denote With1-4alkyl, or the residues R1and R2together form a ring oboznachayut (CH 2)4-5first of all R1and R2independently of one another denote methyl or ethyl, or the residues R1and R2together form a ring and denote (CH2)5.

7. Substituted derivatives of cyclohexane-1,4-diamine according to claim 5, wherein R1and R2together form a ring and denote (CH2)4-5first of all R1and R2together form a ring and denote (CH2)5.

8. Substituted derivatives of cyclohexane-1,4-diamine according to claim 3, wherein R1and R2independently of one another denote With1-4alkyl, first of all, R1and R2independently of one another denote methyl or ethyl.

9. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 3, to 5, characterized in that

R3denotes phenyl, naphthyl, thiophenyl, each of which is either unsubstituted or one-deputizing halogen, or phenyl, attached via a saturated, unsubstituted With1-2alkyl group.

10. Substituted derivatives of cyclohexane-1,4-diamine according to claim 4, wherein R3represents a five-membered sulfur-containing heteroaryl, which is either unsubstituted or one-deputizing halogen, or unsubstituted phenyl, attached through unsubstituted saturated With1-4alkyl group, predpochtitel the but means thiophenyl, which is either unsubstituted or one-deputizing halogen, or phenyl, attached via a saturated, unsubstituted With1-2alkyl group.

11. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, wherein R4denotes N.

12. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, wherein R4denotes N, C(X)R7,

where X denotes O or S, preferably

R4denotes N, C(X)R7,

where X denotes Oh, first of all

R4denotes H or C(O)R7,

where R7preferably denotes N or C1-8alkyl preferably denotes N or C1-3alkyl primarily denotes CH3.

13. Substituted derivatives of cyclohexane-1,4-diamine according to claims 1, 4 or 5, characterized in that

R4and R5together form a five-membered nitrogen-containing heterocyclyl, which is unsaturated, one-deputizing lower alkoxycarbonyl-lower alkyl, halogen or unsubstituted, and which is condensed with the benzene ring.

14. Substituted derivatives of the cycle Alexan-1,4-diamine according to claims 1, 4 or 5, wherein R4denotes N or C1-8alkyl, which is saturated, preferably denotes N or C1-6alkyl, which is on Ishenim, first of all denotes N or C1-3alkyl, which is saturated.

15. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, characterized in that

R5denotes cyclobutyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, anthracene, indolyl, naphthyl, benzofuranyl, benzothiophene, indanyl, benzodioxolyl, acenaphthyl, carbazolyl, phenyl, fluorenyl, fluoranthene, benzothiazolyl, benzotriazolyl, benzo[1,2,5]thiazolyl, 1,2-dihydroanthracene, each of which is unsubstituted or one - or mnogosloinym, first of all

R5denotes cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, anthracene, indolyl, naphthyl, benzofuranyl, benzothiophene, indanyl, benzodioxolyl, acenaphthyl, carbazolyl, phenyl, each of which is unsubstituted or one-deputizing.

16. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, characterized in that

R5means-CHR11R12, -CHR11CH2R12, -CHR11-CH2-CH2R12, -CHR11CH2-CH2-CH2R12, -C(Y)R12where Y denotes O or H2preferably

R5means-CHR11R12, -CHR11CH2R12, -CHR11-CH2-CH2R12, -C(Y)R12where Y represents O.

17. Replacement of the n derivatives of the cyclohexane-1,4-diamine according to one of claims 1 to 3, wherein R11denotes H, C1-4alkyl, which is saturated, branched or unbranched, C(O)O-C1-4alkyl, which is saturated or unsaturated, branched or unbranched, single or mnogosloinym or unsubstituted, preferably denotes H, C1-4alkyl, which is saturated branched or unbranched, or C(O)O-C1-2alkyl, which is saturated, unbranched, single or mnogosloinym or unsubstituted primarily denotes N, CH3With2H5or C(O)O-CH3.

18. Substituted derivatives of cyclohexane-1,4-diamine according to item 16, characterized in that

R12denotes benzofuranyl, benzothiophene, indanyl, benzodioxolyl, carbazolyl, phenyl, benzothiazolyl, benzotriazolyl, benzo[1,2,5]thiazolyl, benzofuranyl, chinoline, ethenolysis, phthalazine or hintline, each of which is unsubstituted or one - or mnogosloinym, first of all

R12represents indolyl, benzofuranyl, benzothiophene, indanyl, benzodioxolyl, carbazolyl, phenyl, each of which is unsubstituted or one - or mnogosloinym.

19. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, characterized in that they are selected from a group including

hydrochloride '-benzyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the hydrochloride of N'-benzyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

hydrochloride 1,N'-dibenzyl-N,N-dimethylcyclohexane-1,4-diamine, non-polar diastereoisomer,

hydrochloride 1,N'-dibenzyl-N,N-dimethylcyclohexane-1,4-diamine, polar diastereoisomer,

the hydrochloride of N-(4-benzyl-4-dimethylaminoethoxy)-N-propylbenzamide,

the hydrochloride of N,N-dimethyl-1-phenyl-N'-propylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl)-N-propylbenzamide, non-polar diastereoisomer,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl)-N-propylbenzamide, polar diastereoisomer,

hydrochloride 1,N'-dibenzyl-N,N,N'-trimethylcyclohexane-1,4-diamine, non-polar diastereoisomer,

hydrochloride 1,N'-dibenzyl-N,N,N'-trimethylcyclohexane-1,4-diamine, polar diastereoisomer,

the hydrochloride of N-(4-benzyl-4-dimethylaminoethoxy)-N-methylbenzamide, polar diastereoisomer,

the hydrochloride of N-(4-benzyl-4-dimethylaminoethoxy)-N-ethylbenzamide, polar diastereoisomer,

the dihydrochloride of 1-benzyl-N'-(1H-indol-3-ylmethyl)-N,N-dimethylcyclohexane-1,4-diamine,

1-benzyl-N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethylcyclohexane-1,4-diamine, CIS/TRANS mixture,

hydrochloride of 1-benzyl-N'-indan-5-yl-N,N-dimethylcyclohex the -1,4-diamine,

the dihydrochloride of 1-benzyl-N'-indan-1-yl-N,N-dimethylcyclohexane-1,4-diamine, CIS/TRANS mixture,

N'-indan-1-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine,

N'-(1H-indol-5-yl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine,

N'-(1H-indol-3-ylmethyl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

N'-(1H-indol-3-ylmethyl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

N'-[2-(1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

N'-[2-(1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

N'-indan-5-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

N'-[2-(5-benzyloxy-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-(N-fluoren-1-yl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine,

the dihydrochloride of N'-indan-2-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-(N-fluoren-9-yl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

1-benzyl-N'-(N-fluoren-9-yl)-N,N-dimethylcyclohexane-1,4-diamine,

N,N-dimethyl-N'-(1-methyl-1H-indol-3-ylmethyl)-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

N,N-dimethyl-N'-(1-methyl-1H-indol-3-ylmethyl)-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-(2-benzo[b]thiophene-3-retil)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-(2-benzo[b]thiophene-3-retil)-1-benzyl-N,N-dimethylcyclohexane-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-acenaphthen-1-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-acenaphthen-1-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[b]thiophene-5-yl-1-benzyl-N,N-dimethylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the hydrochloride of N'-benzo[b]thiophene-5-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzothiazol-6-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[1,2,5]thiadiazole-4-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-adamantane-2-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine,

the dihydrochloride of N'-(9-ethyl-N-carbazole-3-yl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

hydrochloride N'-(3H-benzotriazol-5-yl)-N,N-dimethyl-1-phenylcyclohexane -1,4-diamine, non-polar diastereoisomer,

hydrochloride N'-(3H-benzotriazol-5-yl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-(N-fluoren-9-yl)-N,N-dimethyl-1-thiophene-2-illlogical-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-cyclooctyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine,

the dihydrochloride of N'-(1H-indol-3-ylmethyl)-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-(1H-indol-3-ylmethyl)-]N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-benzo[b]thiophene-3-ylmethyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[b]thiophene-3-ylmethyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

hydrochloride, N'-anthracene-2-yl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[b]thiophene-3-ylmethyl-1-benzyl-N,N-dimethylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[b]thiophene-3-ylmethyl-1-benzyl-N,N-dimethylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)ethyl]-N,N-dimethyl-1-naphthalene-2-illlogical-1,4-diamine, Nepal the RNA the diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)ethyl]N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride methyl-2-(4-dimethylamino-4-phenylcyclohexylamine)-3-(1H-indol-3-yl)propionate, non-polar diastereoisomer,

the dihydrochloride methyl-2-(4-dimethylamino-4-phenylcyclohexylamine)-3-1H-indol-3-yl)propionate, polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-naphthalene-2-illlogical-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-benzo[1,3]dioxol-5-ylmethyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-[2-(6-fluoro-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(6-fluoro-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)ethyl]-N,N,N'-trimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)ethyl]-N,N,N'-trimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride-N,N-N'-[2-(7-methyl-1H-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N,N-dimethyl-N'-[2-(7-methyl-1H-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-[2-(5-fluoro-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(5-fluoro-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N'-acenaphthen-5-ylmethyl-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N'-dimethyl-1-thiophene-2-illlogical-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(1H-indol-3-yl)-1-methylethyl]-N,N-dimethyl-1-thiophene-2-illlogical-1,4-diamine, CIS/TRANS mixture,

the dihydrochloride of N'-[2-(7-benzyloxy-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-cyclooctyl-N,N-dimethyl-1-thiophene-2-illlogical-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-adamantane-2-yl-N,N-dimethyl-1-thiophene-2-illlogical-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of 3-[2-(4-dimethylamino-4-phenylcyclohexylamine)-ethyl]-1H-indol-5-ol, non-polar diastereoisomer,

the dihydrochloride of 3-[2-(4-dimethylamino-4-phenylcyclohexylamine)-ethyl]-1H-indol-5-ol, polar diastereoisomer,

digit the chloride N'-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N'-[2-(5-methoxy-1H-indol-3-yl)ethyl]-N,N-dimethyl-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride of N,N-dimethyl-N'-[2-(5-methyl-1H-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine, non-polar diastereoisomer,

the dihydrochloride of N,N-dimethyl-N'-[2-(5-methyl-1H-indol-3-yl)ethyl]-1-phenylcyclohexane-1,4-diamine, polar diastereoisomer,

the dihydrochloride dimethyl-[1-phenyl-4-(1,3,4,9-tetrahydro-b-carbolin-2-yl)-cyclohexyl]amine,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl)-N-[2-(4-forfinal)ethyl]ndimethylacetamide, non-polar diastereoisomer,

the dihydrochloride methyl ester of 2-(4-dimethylamino-4-phenylcyclohexylamine)-3-(5-fluoro-1H-indol-3-yl)propionic acid, non-polar diastereoisomer,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl)-N-(3-phenylpropyl)ndimethylacetamide, non-polar diastereoisomer,

the dihydrochloride methyl ester of 2-(4-dimethylamino-4-phenylcyclohexylamine)-3-(6-fluoro-1H-indol-3-yl)propionic acid, non-polar diastereoisomer,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl)-2-(1H-indol-3-yl)ndimethylacetamide, polar diastereoisomer,

the dihydrochloride methyl ester of 2-(4-dimethylamino-4-thiophene-2-enciklopedije)-3-(1H-indol-3-yl)propionic acid, non-polar diastereoisomer,

the hydrochloride of N-(4-dimethylamino-4-phenylcyclohexyl-2-(5-methoxy-1H-indol-3-yl)acetamide", she non-polar diastereoisomer,

in the form of their racemates or diastereomers or in the form of mixtures of diastereomers, in any of their ratio in the mixture, in free form or in the form of their physiologically compatible salts, or salts with physiologically compatible acids or cations.

20. Substituted derivatives of cyclohexane-1,4-diamine according to one of claims 1 to 5, wherein R4and R5together do not form a heterocycle.

21. Drug with analgesic effect, containing at least one substituted derivative of cyclohexane-1,4-diamine, characterized in claims 1, 2, 4-18 and optionally containing acceptable additives and/or auxiliary substances and/or optionally other active agents, such as opioid, preferably a potent opioid, primarily morphine, or an anaesthetic, preferably hexobarbital or halothane.

22. Drug, item 21, has analgesic effect, containing at least one substituted derivative of cyclohexane-1,4-diamine, characterized in claim 4, and optionally containing acceptable additives and/or auxiliary substances and/or optionally other active agents, such as opioid, preferably a potent opioid, primarily morphine, or an anaesthetic, predpochtitel what about hexobarbital or halothane.

23. Drug for item 21, has analgesic effect, containing at least one substituted derivative of cyclohexane-1,4-diamine, characterized in claim 5, and optionally containing acceptable additives and/or auxiliary substances and/or optionally other active agents, such as opioid, preferably a potent opioid, primarily morphine, or an anaesthetic, preferably hexobarbital or halothane.

24. Drug, item 21, has analgesic effect, containing at least one substituted derivative of cyclohexane-1,4-diamine, characterized in claim 2 and optionally containing acceptable additives and/or auxiliary substances and/or optionally other active agents, such as opioid, preferably a potent opioid, primarily morphine, or an anaesthetic, preferably hexobarbital or halothane.

25. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 6.

26. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 7.

27. Drug for item 21, characterized in that therein substituted carried the nye cyclohexane-1,4-diamine described in claim 7 or 8.

28. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 9.

29. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 10.

30. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 11.

31. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 12.

32. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 13.

33. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine characterized in 14.

34. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in item 15.

35. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine described in article 16.

36. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diaminoanthraquinone in 17.

37. Drug for item 21, characterized in that contained in the substituted derivatives of cyclohexane-1,4-diamine characterized in p.

38. The method of obtaining substituted derivative of cyclohexane-1,4-diamine according to one of claims 1 to 5, namely, that

a) protected groups S1and S2cyclohexane-1,4-dione of formula II is subjected in the presence of the compounds of formula HNR01R02interaction with cyanide, preferably potassium cyanide, to obtain the protected N-substituted derivative of 1-amino-4-oxo-cyclohexanecarbonitrile formula III

b) aminonitriles formula III is subjected to interaction with ORGANOMETALLIC reagents, preferably Grignard reagent or organolithium reagents of the formula metal-R3with the formation of compounds of formula IVa

the compound of formula IVa otscheplaut protective group S1and S2with the formation of 4-substituted derivative of 4-aminocyclohexanone formula IV

g) 4-substituted derivative of 4-aminocyclohexanone formula IV is subjected to hydroamination compound of the formula HNR04R05with the formation of the derivative of cyclohexane-1,4-diamine of formula V

or 4-substituted derivative of 4-aminocyclohexanone formula IV is subjected to interaction with hydroxylamine and after the formation of the corresponding oxide, restore to the formation of compounds of formula I, where, if necessary, at each of the stages a)to d) reactive groups not involved in the reaction, can be protected, followed by removal of the optionally introduced protective groups,

thus R1, R2, R3R4and R5have specified in claim 1 values, and

R01and R02independently of one another denote C1-8alkyl, or R01and R02together form a ring and denote CH2CH2NR6CH2CH2or (CH2)3-6where R6represents C1-8alkyl, R04denotes a protective group, or With1-8alkyl, which is saturated,

R05stands With3-8cycloalkyl, aryl or 5-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and condensed with one or two benzene rings, each of which is unsubstituted or one-deputizing, Deputy selected from halogen, lower alkyl, lower alkoxy, hydroxy or benzyloxy; or-CHR11R12, -CHR11-CH2R12, -CHR11-CH2-CH2R12, -CHR11 -CH2-CH2-CH2R12, -C(Y)R12,

where Y denotes H2,

R11denotes H, C1-7alkyl, which is saturated branched or unbranched, and

R12denotes phenyl or a five-membered heteroaryl containing 1-3 heteroatoms selected from nitrogen, oxygen or sulfur, and

condensed with one or two benzene rings, each of which is unsubstituted or one - or mnogosloinym,

thus the values of R11and R12the substituents of the alkyl, phenyl or heteroaryl selected from halogen, lower alkyl, lower alkoxy, hydroxy, trifloromethyl or benzyloxy;

or

R04and R05together form a five-membered azotsoderzhashchie a heterocycle, which is unsaturated, one-deputizing lower alkoxycarbonyl-lower alkyl, halogen or unsubstituted, and which is condensed with benzene ring, and

S1and S2independently from each other represent a protective group or together represent a protective group, preferably monoacetal.

39. The method of obtaining substituted derivative of cyclohexane-1,4-diamine according to 38, characterized in that hydroamination in stage d) is carried out in the presence of ammonium formate, ammonium acetate or NaCNBH3

40. The method of obtaining substituted derivative of cyclohexane-1,4-diamine according to 38, characterized in that when interacting with cyanide use TMC-CN.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-aminocyclohexanol of the general formula (I) being optionally as their physiologically acceptable salts and first of all physiologically compatible acids. In compound of the general formula (I) R1 and R2 mean independently of one another hydrogen atom (H) or (C1-C8)-alkyl that can be saturated or unsaturated but both R1 and R2 can't mean simultaneously H, or residues R1 and R form a ring in common and mean (CH2)3-6; R2 means unsubstituted phenyl or phenyl substituted with halogen atom that is added through saturated or unsaturated, branched or linear (C1-C4)-alkyl group; R4 means heteroaryl chosen from 5-membered heteroaryl wherein heteroatoms are chosen from nitrogen, oxygen or sulfur atoms and each of these atoms is condensed with benzene ring and means unsubstituted or monosubstituted (C1-C8)-alkyl; -CHR6R7, -CHR6-CH2R7, -CHR6-CH2-CH2R7, -CHR6-CH2-CH2-CH2R7 wherein R6 represents H; R7 represents phenyl that can be unsubstituted or mono- either multi-substituted with halogen atoms. Also, invention relates to a method for synthesis of compounds of the formula (I) and a medicinal agent based on thereof. Synthesized compounds can be sued for preparing a medicinal agent designated for treatment of pain being first of all acute, visceral, neuropathic or chronic pain, and to a medicinal agent designated for treatment of diseases mediated by function of ORL1-receptor, for example, such as fear state, epilepsy, cardiovascular diseases.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and drug.

10 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein A means benzene ring optionally substituted with one or more the following groups: -OR2 wherein R2 mean linear or branched (C1-C5)-alkyl; X means -CH=, -CH2-, -N= or -NH-radical; Y means radical -CH2, oxygen or sulfur atom or group -NR7 wherein R7 means hydrogen atom or linear or branched (C1-C5)-alkyl; R1 means hydrogen atom, linear or branched (C1-C5)-alkyl, and to pharmaceutically acceptable salts also. Also, invention relates to a pharmaceutical composition showing anti-diabetic activity. The pharmaceutical composition comprises compound of the general formula (I) as an active component and an inert excipient. Invention provides bicyclic derivatives of guanidine eliciting anti-diabetic activity.

EFFECT: valuable medicinal properties of compounds and composition.

8 cl, 2 tbl, 4 ex

The invention relates to derivatives of 2-phenyl-benzo(b) furan and thiophene, which may be suitable for the treatment of dependent estrogenos diseases, such as prostatic hyperplasia, breast cancer, endometrial cancer, populating infertility and melanoma

The invention relates to the field of organic synthesis and relates to new organic compounds, method of their obtaining for several options and pharmaceutical compositions containing these compounds

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to using compounds of the general formula (I): and their pharmaceutically acceptable acid-additive salts. Compounds are used for preparing medicinal agents used in treatment diseases and state associated with system of adenosine receptors A2A, such as Alzheimer's disease, Parkinson's diseases, Huntington's syndrome, schizophrenia, anxiety state, pain, depression, narcomania to such substances as amphetamine, cocaine, opioides, ethyl alcohol, nicotine, cannabinoids, or in treatment of hypoxia, ischemia, epileptic attack. Also, proposed compounds exert neuroprotective effect and can be used as sedative, antipsychotic or anti-epileptic agents.

EFFECT: valuable medicinal properties of compounds.

18 cl, 1 tbl, 49 ex

The invention relates to new compounds of the formula (I), where a represents the group CH2or atom That denotes H or halogen, D is CH2, OCH2, NHCH2CH2CH2, R denotes phenyl, benzothiazolyl, indolyl, indazoles, purinol, pyridyl, pyrimidyl, thiophenyl, each of these groups may be substituted or unsubstituted

The invention relates to new guanidinium heterocyclic compounds of the formula (I), where R1denotes H, alkyl or is absent when R1missing link (a) is a double bond, D represents CR2, R2selected from H, alkyl, halogen, or, when is a CR3D can be N, denotes NR9, CR3=CR8, CR3, S, where R9denotes H, alkyl, alkenyl or quinil and where R3and R8selected from H, alkyl, alkenyl, quinil or cyano, R4, R5, R6each independently selected from H, alkyl, alkenyl, quinil, cyano, halogen or NH-C(= NR10)OTHER11(guanidine), R10and R11selected from H, methyl and ethyl, and where only one of R1, R5and R6is guanidines, R7selected from H, alkyl, alkenyl, quinil and halogen

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-aminocyclohexanol of the general formula (I) being optionally as their physiologically acceptable salts and first of all physiologically compatible acids. In compound of the general formula (I) R1 and R2 mean independently of one another hydrogen atom (H) or (C1-C8)-alkyl that can be saturated or unsaturated but both R1 and R2 can't mean simultaneously H, or residues R1 and R form a ring in common and mean (CH2)3-6; R2 means unsubstituted phenyl or phenyl substituted with halogen atom that is added through saturated or unsaturated, branched or linear (C1-C4)-alkyl group; R4 means heteroaryl chosen from 5-membered heteroaryl wherein heteroatoms are chosen from nitrogen, oxygen or sulfur atoms and each of these atoms is condensed with benzene ring and means unsubstituted or monosubstituted (C1-C8)-alkyl; -CHR6R7, -CHR6-CH2R7, -CHR6-CH2-CH2R7, -CHR6-CH2-CH2-CH2R7 wherein R6 represents H; R7 represents phenyl that can be unsubstituted or mono- either multi-substituted with halogen atoms. Also, invention relates to a method for synthesis of compounds of the formula (I) and a medicinal agent based on thereof. Synthesized compounds can be sued for preparing a medicinal agent designated for treatment of pain being first of all acute, visceral, neuropathic or chronic pain, and to a medicinal agent designated for treatment of diseases mediated by function of ORL1-receptor, for example, such as fear state, epilepsy, cardiovascular diseases.

EFFECT: improved method of synthesis, valuable medicinal properties of compounds and drug.

10 cl, 1 tbl, 21 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of sulfonamide of the general formula (I): wherein A means a substitute chosen from 5- or 6-membered heteroaromatic ring comprising 1 or 2 heteroatoms chosen from oxygen (O), nitrogen (N) or sulfur (S) optionally substituted with 1 or 2 halogen atoms, (C1-C4)-alkyl or phenyl radical, or 5- or 6-membered heteroaryl radical comprising 1 or 2 atoms of O, N or S; bicyclic heteroaromatic ring comprising from 1 to 3 heteroatoms chosen from O, N or S and optionally substituted with 1 or 2 halogen atoms or (C1-C4)-alkyl; R1 means hydrogen atom (H), (C1-C4)-alkyl, benzyl; n means 0, 1, 2, 3 or 4; R2 means -NRR5 or the group of the formula: wherein a dotted line means optional chemical bond; R, R4 and R5 mean independently H or (C1-C4)-alkyl; or one of its physiologically acceptable salts. Compounds of the formula (1) possess antagonistic activity with respect to serotonin HT6-receptors that allows their using in pharmaceutical composition and for preparing a medicament.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

10 cl, 2 tbl, 7 ex

.FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their physiologically acceptable salts also possessing properties for decrease the blood sugar content. In compound of the formula (I) A means phenyl wherein phenyl residue can be substituted up to three times with fluorine (F), chlorine (Cl) and bromine (Br) atoms; R1 and R2 mean hydrogen atom (H); R3, R4, R5 and R6 mean independently of one another H, F, Cl, Br, -NO2, -O-(C1-C6)-alkyl, (C1-C6)-alkyl, -COOH; R7 means H, (C1-C6)-alkyl wherein alkyl can be substituted up to three times with -OH, -CF3, -CN, COOH, -COO-(C1-C6)-alkyl, -CO-NH2, -NH2, -NH-(C1-C6)-alkyl, -N-[(C1-C6)-alkyl]2, -NHCO-(C1-C6)-alkyl, -NHCOO-(C1-C6)-alkyl or -NHCOO-(C1-C4)-alkylenephenyl; in (CH2)m m can mean 0-6 and aryl means phenyl, O-phenyl, CO-phenyl, benzo[1,3]dioxolyl, pyridyl, indolyl, piperidinyl, tetrahydronapthyl, 2,3-dihydrobenzo[1,4]dioxynyl, benzo[1,2,5]thiadiazolyl, pyrrolidinyl, morpholinyl wherein aryl residue can be substituted mono- or multiple with R9 wherein R9 means F, Cl, Br, -OH, -NO2, -CF3, -OCF3, (C1-C6)-alkyl, (C1-C6)-alkyl-OH, -O-(C1-C6)-alkyl, -COOH, -COO-(C1-C6)-alkyl. Also, invention relates to a pharmaceutical composition and a method for preparing a medicinal agent.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

7 cl, 2 sch, 1 tbl, 293 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein A means benzene ring optionally substituted with one or more the following groups: -OR2 wherein R2 mean linear or branched (C1-C5)-alkyl; X means -CH=, -CH2-, -N= or -NH-radical; Y means radical -CH2, oxygen or sulfur atom or group -NR7 wherein R7 means hydrogen atom or linear or branched (C1-C5)-alkyl; R1 means hydrogen atom, linear or branched (C1-C5)-alkyl, and to pharmaceutically acceptable salts also. Also, invention relates to a pharmaceutical composition showing anti-diabetic activity. The pharmaceutical composition comprises compound of the general formula (I) as an active component and an inert excipient. Invention provides bicyclic derivatives of guanidine eliciting anti-diabetic activity.

EFFECT: valuable medicinal properties of compounds and composition.

8 cl, 2 tbl, 4 ex

The invention relates to inhibitors tyrosinekinase type bis-indolylmaleimide compounds of the formula I

< / BR>
where Z denotes a group of General formula II

< / BR>
where A, B, X, Z, R1-R10have the meanings indicated in the claims, as well as the way they are received and drug based on these compounds

The invention relates to new derivatives of amides and urea of the formula I

R1-(CH2)n(Y)q-(Z)r-CO-NH-R2(I)

in which R1- 3-indolyl, unsubstituted or monosubstituted, AO, Hal, CN;2represents a

< / BR>
< / BR>
or

< / BR>
m = 1 or 2; n = 0, 1, 2, 3 or 4; Y is 2,4-cyclohexylamine, 1,3 - pyrrolidinone, 1,4-piperazinone or 1,4-piperidinylidene ring, which may also be partially digidrirovanny; Z - (CH2)nNH-, q = 0 or 1; r = 0 or 1; R3- A; R4- AO; Hal Is F, Cl, Br, J; A - unbranched or branched C1-C6alkyl, provided that q and r are not simultaneously equal to 0, and their physiologically acceptable salts

New benzamidomethyl // 2189973
The invention relates to new derivatives of benzamidomethyl formula (I), where R1- phenyl, naphthalene, quinoline, isoquinoline, tetrahydroquinoline, tetrahydroisoquinoline, pyridine, hinzelin, cinoxacin, and aromatic and heteroaromatic ring can be substituted by the radicals R4; R2is hydrogen, chlorine, bromine, fluorine, alkyl, -NHCO-naphthyl, -NHSO2- C1-4-alkyl, -O-C1-4-alkyl, -CO-NH - C1-4-alkyl, NO2; R3is a hydrocarbon residue with 1 to 6 carbon atoms, which may carry cycloalkyl, indolenine, phenyl ring, or a residue group-SCH3-; R4- alkyl, -O-C1-4-alkyl, chlorine, fluorine, bromine, iodine, CF3, pyridine; X is a bond, - (CH2)m-, - (CH2)m-O-(CH2)0-, - (CH2)m-S-(CH2)o-, - (CH2)m-SO- (CH2)o-, - (CH2)m-SO2- (CH2)0-, -CH=CH-, -CC-, -CO-CH=CH-, -CH= CH-CO-, - (CH2)m-CO-(CH2)0-, - (CH2)m-NR5CO-(CH2)0-, (R5=H, C1-4-alkyl), - (CH2)m- CONR5-(CH2)0-, - (CH2)m-NHSO2-(CH2)0-, - (CH2)m-SO2NH-(CH2)0-, -N

The invention relates to benzonitrile and benzalconium formula I, where AG - means one or twice substituted with CN and/or F phenyl residue; Q meansnH2n; n denotes 3 or 4; and their salts accession acids, except for 3-/4-(4-fluoro-phenyl)-1-piperazinil)butyl/-5-cyan-indole and 3-4-(4-(2-fluoro-phenyl)-1-piperazinil)butyl/-5-cyan-indole, but not their salts accession acids

The invention relates to an improved process for the preparation of substituted indole derivatives useful in the treatment and prevention of migraine

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 1,2-diaminopentane of the formula (I): wherein R1 means hydrogen atom, (C1-C6)-alkyl; R2 means phenyl-(C1-C6)-alkyl wherein phenyl is substituted with halogen atom; R3 means hydrogen atom; R4 means -W-X-Y-Z wherein W is absent or means (C1-C6)-alkylene; X is absent or means -S(O)n- or -N(Ra)-; Y means arylene or heteroarylene; Z means hydrogen atom, aryl; Ra means hydrogen atom; n = 0 under condition that this enumeration doesn't involve trans-3,4-dichloro-N-[2-(dimethylamino)cyclopentyl]benzamide and trans-N-methyl-3,4-dichloro-N-[2-(dimethylamino)cyclopentyl]benzamide, or its pharmaceutically acceptable salt. Also, invention proposes a pharmaceutical composition possessing antagonistic activity with respect to CCR-3 receptors and comprising the effective amount of compound of the formula (I) or its salt and excipient. Invention provides using derivatives of 1,2-diaminopentane inhibiting binding eotaxine with CCR-3 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

27 cl, 1 tbl, 17 ex

FIELD: medicine, pharmaceutical industry and technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing a drug possessing analgesic, antipyretic and psychostimulating effect. The drug possessing analgesic, antipyretic and psychostimulating effect comprises paracetamol, propiphenazone and anhydrous caffeine as an active components, and starch, microcrystalline cellulose, magnesium stearate, copolyvidon, hydroxypropylmethylcellulose, sodium dodecyl sulfate, crospovidon and croscarmelose sodium as accessory substances taken in the definite ratio of components. Method for preparing a drug possessing analgesic, antipyretic and psychostimulating effect involves stirring sieved powders of paracetamol, propiphenazone, anhydrous caffeine and microcrystalline cellulose followed by wetting the prepared mixture with hydroxypropylcellulose solution and repeat stirring to uniform moisture distribution. Then method involves the successive granulation, drying, powdering prepared granules with a mixture of copolyvidon, dodecyl sodium sulfate, starch, croscarmelose sodium and magnesium stearate to obtain a homogenous mass followed by the tabletting process the prepared homogenous mass. The drug prepared by above described method is made as a tablet and possesses the high dissolving index and the high dosing precision.

EFFECT: improved preparing method of drug.

3 cl, 2 tbl, 1 ex

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